Cascade impactors are utilized to determine the aerodynamic particle size distribution and mass concentration levels of solid particulates and liquid aerosols from aerosolized dry powder and aerosolized liquid drug samples that are injected into the cascade impactor. Cascade impactors are also used by the environmental control and monitoring industry in order to determine particulate distributions derived from air samples. One reason for using cascade impactors in a testing environment is that the air flowing through a cascade impactor simulates the air flowing through the human lung. When delivering drugs through the respiratory tract and into the human lung, whether the drug is in the form of microionized powders or in the form of micron-sized droplets of an aerosolized mist from a solution, it is important to know the particle size distribution of the drug.
Only drug particles having a size generally less than five microns in diameter can penetrate deep into the lungs and bronchi. Larger particles will be ingested and then excreted from the body. The deep lung tissue provides an enormous amount of surface area for the active drug substance to get absorbed into the blood-stream and thus permits the efficacious use of lower drug doses to obtain the same or better physiological responses than is capable from drug deliveries by oral means. The measurement of the particle size distribution from the injection of the drug into the cascade impactor is called a dose determination. Dose determination data from a cascade impactor is an integral part of a submission to the FDA as part of an NDA or New Drug Application. Thousands of dose determinations need to be done in order to meet the FDA's submission criteria for a new inhalation drug, and subsequent to the drug approval, thousands of tests are also needed, to be performed over the lifetime of the inhalation drug, as an ongoing quality control measure, in order to continuously demonstrate to the FDA that the performance of the inhalation drug continues to meet the approval criteria or standards for the drug.
While numerous conventional cascade impactors are known and in commercial use, probably the most popular or most commonly used cascade impactor is the Anderson cascade impactor. However, obtaining a dose determination from an Anderson cascade impactor is very labor intensive, error prone, time-consuming, and thus, a very expensive process. For example, or more particularly, conventional procedures for obtaining particle size distribution data using conventional cascade impactors involves very low throughput results since conventional impactors require manual set-up procedures, operations, testing, and dose determination. There are many component parts that need to be carefully disassembled and washed during the use of a conventional cascade impactor in order to obtain a dose determination. Samples must be manually and very carefully collected from the various impactor components, and those components must then be manually assembled in preparation for conducting another dose determination. In addition, the manual process is very prone or susceptible to significant degrees of operator-induced variabilities impacting the generated data. Each operator, that is, lab technician, analyst, or the like, washes or cleans the various components of the cascade impactor in different ways or modes thus causing inconsistencies in the amounts of the drug collected from each impactor stage and from each impactor plate. This inconsistent human washing or cleaning of the plurality of impactor surfaces of the plurality of impactor stages further affects the recovery of the particular drug from the same apparatus for subsequent dose determinations. These operator-induced variabilities can precipitate the need for additional dose determinations to be performed which therefore cause delays in connection with the submission of the dose determination data by the drug companies to the FDA, and therefore, obviously result in delays in the approval of the particular drugs by the FDA. Such delays, of course, can cause the loss of millions of dollars in lost revenue to the drug companies.
Continuing still further, it is to be appreciated that a conventional Anderson cascade impactor comprises a plurality of impactor stages consisting of a plurality of fluid jets or orifices formed within the impactor stages. The particular number of impactor stages or impactor plates used to make up a column of the Anderson cascade impactor is variable and may depend upon the particular drug and the particle size ranges to be measured. The impactor stages are disposed within a vertically stacked array with succeeding impactor stages comprising smaller orifice diameters. Within each impactor stage, there is provided an impactor plate. During a dosing operation, as the drug, suspended within an aerosol stream, is delivered into the throat of the impactor and is subsequently conducted into the impactor stages, the aerosol stream impacts the impactor plate. During a dosing operation, as the drug, suspended within an aerosol stream, is delivered into the throat of the impactor and is subsequently conducted into the impactor stages, the aerosol stream impacts the first one of the impactor plates. Based upon the particle velocity and mass, particles with higher momentum adhere to the first impactor plate. Particles with insufficient momentum bounce up from the first impactor plate so as to go through the succeeding impactor stage disposed beneath the first impactor plate. Each impactor stage is provided with a multitude of orifices of the same diameter, however, succeeding impactor stages are provided with orifices of progressively smaller diameters. Accordingly, as the particles travel through succeeding impactor stages, they gain velocity and hence momentum and settle upon successive impactor plates. Thus, particles of different size ranges or diameters are collected mostly upon the impactor plates while other or remaining particles within the aerosol stream collect upon the impactor stages, thereby inherently providing the impactor with the desired or requisite separation capabilities of the particles within the aerosol stream by means of particle size.
Accordingly, the automated cascade impactor system, as disclosed within the aforenoted U.S. Pat. No. 7,926,367, and the aforenoted U.S. patent application Ser. No. 12/929,051, was developed so as to effectively overcome the various previously noted operational drawbacks characteristic of the aforenoted conventional manually operated cascade impactors. However, while the aforenoted automated cascade impactor has effectively revolutionized dose determination technology and the industry that performs dose determinations in support of, for example, NDAs presented to the FDA for approval, further improvements were deemed necessary or desired. For example, it was desired to improve the collection efficiency of the drug. In addition, it was desired to implement a system wherein the amount of solvent used was capable of being significantly reduced. Still further, it was desired to implement a system wherein the drug could be collected separately from impactor plates of the impactor stages in addition to, or in lieu of, collection of the drug from the impactor stages per se.
A need therefore exists in the art for a new and improved automated cascade impactor wherein the collection efficiency of the drug could be improved, wherein the amount of solvent used was capable of being significantly reduced, and wherein the drug could be collected separately from the impactor plates of the impactor stages in addition to, or in lieu of, collection of the drug from the impactor stages per se.